1. Field of the Invention
The present invention is concerned with the production of 1,2,3-triazoles by a simple, economical and safe method.
The unsubstituted 1,2,3-triazole is utilized in the preparation of important pharmaceutical compounds such as the beta-lactamase inhibitor, Tazobactam (Ger. Offen. DE 2943427, 800508 EP 331395 AI 890906). The substituted triazoles can be used as intermediates in the preparation of various other pharmaceuticals or pesticides (JP 05222006 A2 930831 Heisei, JP 05148280 A2 930615 Heisei, JP 05112536 A2 930507 Heisei and EP 433842 A2 910626).
2. Description of Related Art
One of the current methods used for the preparation of triazoles is by the reaction of acetylene and azide derivatives followed by reductive cleavage of the protecting group (Japan Kokai Tokyo Koho JP 1-143861). The chemicals used have an explosive nature and the process employs hazardous conditions.
Another method of preparation utilizes dichloroacetaldehyde and sulfonyl hydrazide (Japan Kokai Tokyo Koho JP 5-140121). The preparation requires two steps. The reactions used are summarized below: ##STR1##
The above process has the following disadvantages:
1. It employs dichloroacetaldehyde, that is toxic and has a tendency to polymerize in the presence of acids and also on storage. PA1 2. The process requires two steps and these two steps require two different solvents. PA1 3. The removal of propionic acid (the solvent) from the hydrazone product of the first step is difficult on a production scale. The removal requires large amounts of hexane to wash out the propionic acid. PA1 4. Any remaining propionic acid leads to the formation of side products that contaminate the final product. PA1 5. The described method requires the isolation of triazoles using column chromatography and this increases cost, particularly for large scale preparations. PA1 1. It utilizes dihaloethanediol instead of dichloroacetaldehyde. Dihaloethanediol is less toxic and does not tend to polymerize on standing over a long period of time. PA1 2. The method provides a one pot synthesis process. PA1 3. The method utilizes one solvent for both steps and needs no isolation and further purification of the intermediate hydrazone, generated in situ. This intermediate can also be isolated easily in pure form and can be used for the synthesis of other N-substituted triazoles. PA1 4. In addition to sulfonyl hydrazides, readily available and cheaper substituted carboxylic acid hydrazides can also be used.